Discovery of <i>N</i>-<scp>l</scp>-Lactoyl-<scp>l</scp>-Trp as a Bitterness Masker via Structure-Based Virtual Screening and a Sensory Approach

Abstract

<i>N</i>-Lactoyl-amino acid derivatives (<i>N</i>-Lac-AAs) are of increasing interest as potential taste-active compounds. The complexity and diversity of <i>N</i>-Lac-AAs pose a significant challenge to the effective discovery of taste-active <i>N</i>-Lac-AAs. Therefore, a structure-based virtual screening was used to identify taste-active <i>N</i>-Lac-AAs. Virtual screening results showed that <i>N</i>-lactoyl-hydrophobic amino acids had a higher affinity for taste receptors, specifically <i>N</i>-l-Lac-l-Trp. And then, <i>N</i>-l-Lac-l-Trp was synthesized in yields of 22.3% by enzymatic synthesis in the presence of l-lactate and l-Trp, and its chemical structure was confirmed by MS/MS and one-dimensional (1D) and two-dimensional (2D) NMR. Sensory evaluation revealed that <i>N</i>-l-Lac-l-Trp had a significant taste-masking effect on quinine, d-salicin, caffeine, and l-Trp, particularly l-Trp and caffeine. <i>N</i>-l-Lac-l-Trp had a better masking effect on the higher concentration of bitter compounds. It reduced the bitterness of caffeine (500 mg/L) and l-Trp (1000 mg/L) by approximately 20 and 26%, respectively. The result of the ligand-receptor interaction and a quantum mechanical analysis showed that <i>N</i>-l-Lac-l-Trp increased the binding affinity to the bitter receptor mainly through hydrogen bonding and lowering the electrostatic potential.